OBJECTIVE: Numerous macrolide metabolites of bacterial or mold origin exhibit varying antimicrobial activities and some of them (e.g., ansamycins) are highly promising potential antitumor agents. We plan to establish a genera scheme leading to total syntheses of several representative macrolide antibiotics and also to develop new synthetic methodologies required to execute vital transformations. The macrolides chosen for this purpose are (A) 14-membered "polyoxo" antibiotics, pikromycin and 6-desoxyerythronolide (a metabolite isolated as a biosynthetic precursor of erythromycins), (B) 16-membered homologs, leucomycin-A1 and tylosin, and (C) cytochalasins A, B, and F, cytostatically active metabolites. If the knowledge acquired from these studies proves to be sufficient, a total synthesis of ansamycin will be contemplated. In addition we intend to utilize synthetic intermediates and modified antibiotics to elucidate later stages of biosynthesis of macrolide antibiotics, in particular, that leucomycin.